Association of Mutant KRAS Alleles With Morphology and Clinical Outcomes in Pancreatic Ductal Adenocarcinoma.

CONTEXT.­: Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood. OBJECTIVE.­: To characterize the potential morphologic and clinical outcome differences in PDACs harboring distinct mutant KRAS alleles. DESIGN.­: Cohort 1 consisted of 127 primary conventional PDACs with no neoadjuvant therapy, excluding colloid/mucinous, adenosquamous, undifferentiated, and intraductal papillary mucinous neoplasm-associated carcinomas, for which an in-house 42-gene mutational panel had been performed. A morphologic classification system was devised wherein each tumor was assigned as conventional, papillary/large duct (P+LD, defined as neoplastic glands with papillary structure and/or with length ≥0.5 mm), or poorly differentiated (when the aforementioned component was 60% or more of the tumor). Cohort 2 was a cohort of 88 PDACs in The Cancer Genome Atlas, which were similarly analyzed. RESULTS.­: In both cohorts, there was significant enrichment of P+LD morphology in PDACs with KRAS G12V and G12R compared with G12D. In the entire combined cohort, Kaplan-Meier analyses showed longer overall survival (OS) with KRAS G12R as compared with G12D (median OS of 1255 versus 682 days, P = .03) and in patients whose PDACs displayed P+LD morphology as compared with conventional morphology (median OS of 1175 versus 684 days, P = .04). In the adjuvant-only subset, KRAS G12R had the longest OS compared with G12D, G12V, and other alleles (median OS unreached/undefined versus 1009, 1129, and 1222 days, respectively). CONCLUSIONS.­: PDACs with different mutant KRAS alleles are associated with distinct morphologies and clinical outcomes, with KRAS G12R allele associated with P+LD morphology and longer OS when compared with G12D using Kaplan-Meier studies.

Clinical Outcomes of Rhegmatogenous Retinal Detachment Repair in Patients with Nystagmus.

PURPOSE: To report the anatomical and visual outcomes of rhegmatogenous retinal detachment (RRD) repair in patients with congenital or acquired nystagmus. METHODS: This was a case series involving a retrospective review of medical records from January 1st, 2015, to April 1st, 2021 of 8 eyes of 8 patients (7 male, 1 female) with documented nystagmus who underwent RRD repair. Primary outcomes included final re-attachment rate and single surgical anatomic success (SSAS) at three months postoperatively. Secondary outcomes included final visual acuity and mean number of additional procedures required for retinal re-attachment. RESULTS: Mean age was 52.1 years (range: 14 to 77 years) and mean follow-up time was 18.6 months (range: 2.8 to 32.9 months). Pars plana vitrectomy (PPV) was performed in 4 patients (50.0%), scleral buckle (SB) in 3 (37.5%), and PPV-SB in 1 (12.5%). A repeat PPV was required in 3 eyes (37.5%) due to proliferative vitreoretinopathy (PVR), 2 of which initially underwent PPV and 1 had PPV/SB. Two eyes (25%) required a third PPV due to PVR or retinal breaks. Mean time to first re-detachment was 29 days. SSAS at 3 months was achieved in 5 patients (62.5%). Complete final retinal re-attachment was achieved in all patients. Final visual acuity improved or stabilized in 7 eyes (87.5%). CONCLUSIONS: Despite a 100% final retinal re-attachment rate, RRD repair can be challenging among patients with nystagmus, including postoperative complications such as recurrent retinal detachment due to retinal breaks. No silicone oil emulsification or related complications were observed in our series.

Risk Factors for Epiretinal Membrane After Rhegmatogenous Retinal Detachment Repair: Quantitative Ultra Widefield Imaging Analysis.

BACKGROUND AND OBJECTIVE: To utilize quantitative ultra widefield retinal imaging to investigate the risk factors associated with the incidence and severity of postoperative epiretinal membrane (ERM) in patients who underwent primary rhegmatogenous retinal detachment (RRD) repair. PATIENTS AND METHODS: This retrospective study included patients who underwent pars plana vitrectomy (PPV) with scleral buckle (SB) for RRD, without a prior history of ERM, and who underwent ultra widefield imaging postoperatively between June 2020 and February 2022. The size and location (distance from the macula) of the drainage retinotomy and the area of peripheral pathology, including retinal breaks and laser scars, were quantitatively measured with cloud-based software. The severity of postoperative ERM formation at 6 months was graded from grade 1 to 4. We investigated the risk factors that were significantly associated with the incidence and severity of postoperative ERM at 6 months. RESULTS: We included 80 eyes (80 patients) in this study. Postoperative ERM developed in 37 eyes (46%) at 6 months. The severity of ERM was grade 1 in 24 eyes (65%), grade 2 in 6 eyes (16%), grade 3 in 4 eyes (11%), and grade 4 in 3 eyes (8%). Postoperative ERM was not associated with the presence or the location of drainage retinotomy (P = 0.836 and 0.820, respectively). However, it was significantly associated with larger surface area of drainage retinotomy (P = 0.039). In addition, postoperative ERM was significantly associated with a larger area of peripheral pathology (P = 0.012), a larger extent of RRD (P = 0.013), vitreous hemorrhage (P = 0.026), redetachment within 6 months (P = 0.022), use of silicone oil as a tamponade (P = 0.047), and number of surgeries within 6 months (P = 0.027). These factors, in addition to 360° endolaser, were also significantly associated with the severity of postoperative ERM. In multivariable linear regression analysis, the only variable that remained statistically significant was the size of the drainage retinotomy (P = 0.023). CONCLUSION: The pathogenesis of postoperative ERM is multifactorial. Large drainage retinotomies may increase the risk of ERM formation. [Ophthalmic Surg Lasers Imaging Retina 2023;54:206-216.].

Outcomes of Laser Retinopexy for Retinal Tears in Pseudophakic Eyes with Multifocal Versus Monofocal Intraocular Lenses: A Matched Cohort Study.

PURPOSE: Performing laser retinopexy through multifocal intraocular lenses may be challenging due to aberrations of the peripheral retinal view. This study investigated the influence of multifocal versus monofocal intraocular lenses on outcomes of laser retinopexy for retinal tears. METHODS: Pseudophakic eyes (multifocal and monofocal intraocular lenses) that underwent in-office laser retinopexy for retinal tears, with a minimum follow-up of 3 months, were retrospectively analyzed. Eyes with multifocal intraocular lenses were matched to controls with monofocal intraocular lenses in a 1:2 ratio for age, gender, number, and location of retinal tears. The main outcome measure was the rate of complications. RESULTS: We included 168 eyes in the study. Fifty-six eyes (51 patients) with multifocal intraocular lenses were matched with 112 eyes (112 patients) with monofocal intraocular lenses. The mean follow-up was 26 months. Baseline characteristics were similar between two groups. No significant differences were noted in the rate of successful laser retinopexy without additional procedures (91% vs. 86% at 3 months and 79% vs. 74% during follow-up, in the multifocal intraocular lens and monofocal intraocular lens group, respectively). No significant differences were observed in the rate of subsequent rhegmatogenous retinal detachment (multifocal, 4% vs. monofocal, 6%, p=.716) or need for additional laser retinopexy for new tears (14% vs. 15%; p=.939). The surgery rates for vitreous hemorrhage (0% vs. 3%; p=.537), epiretinal membrane (2% vs. 2%; p=.553), and vitreous floaters (5% vs. 2%, p=.422) were not significantly different. Visual outcomes were also similar. CONCLUSION: Multifocal intraocular lenses did not appear to negatively impact the outcomes of in-office laser retinopexy for retinal tears.

Factors Associated with Fluctuations in Central Subfield Thickness in Patients with Diabetic Macular Edema Using Diabetic Retinopathy Clinical Research Protocols T and V.

Purpose: To identify baseline ocular and systemic factors associated with central subfield thickness (CST) fluctuations in patients with diabetic macular edema (DME) using data from Diabetic Retinopathy Clinical Research Protocols T and V. Design: Post hoc analysis of clinical trial databases. Subjects: Patients in Protocols T and V. Methods: The standard deviation (SD) of all recorded CSTs for each patient during each Protocol's study period was calculated. The CST SD (corresponding to CST fluctuations) for each patient was analyzed against baseline ocular and systemic factors using linear regression analyses. Each Protocol was analyzed separately. Main Outcome Measures: Factors associated with CST fluctuations. Results: A total of 1197 eyes of 1197 subjects were included. In Protocol T (559 eyes, mean CST SD was 56.4 ± 35.1 microns), using multivariate linear regression analysis, baseline urine albumin/creatine ratio (for every 1000 mg/g, CST point estimate 3.50, 95% confidence interval [CI] 0.58 to 6.43, P = 0.0190), and baseline CST (for every 10 microns, 0.87, 95% CI 0.58 to 1.16, P < 0.0001) were positively associated with CST fluctuations. Baseline visual acuity (for every 10 ETDRS letters, -9.52, 95% CI -11.89 to -7.15, P < 0.0001) was negatively associated with CST fluctuations. In Protocol V (638 eyes, mean CST SD 36.6 ± 28.4 microns), gender (female, 2.18, 95% CI 0.30 to 4.06, P = 0.0227), baseline CST (for every 10 microns, 2.51, 95% CI 2.21 to 2.82, P < 0.0001), systolic blood pressure (for every 1 mm of mercury, 0.11, 95% CI 0.01 to 0.21, P = 0.0261), and observation with deferred anti-VEGF injections (5.04, 95% CI 2.51 to 7.58, P < 0.0001) were positively associated with CST fluctuations. Type 2 diabetes (-7.37, 95% CI -13.64 to -1.11, P = 0.0209) and prompt anti-VEGF injections (-6.51, 95% CI -9.07 to -3.96, P < 0.0001) were negatively associated with CST fluctuations. Conclusions: Worse visual acuity at baseline, baseline renal disease, hypertension, female gender, type 1 diabetes, and delayed anti-VEGF treatment may be associated with increased CST fluctuations in patients with DME. Addressing these parameters may limit CST fluctuations and help identify patients requiring more frequent monitoring or treatment.

Euglycemic diabetic ketoacidosis (EDKA) after pancreaticoduodenectomy: An under-recognized metabolic abnormality with outcome implications.

BACKGROUND: Euglycemic diabetic ketoacidosis is a metabolic condition characterized by relative euglycemia, ketonemia, and metabolic acidosis that occurs through mechanisms resembling starvation. Pancreaticoduodenectomy is a complex abdominal operation that subjects patients to a prolonged fasting and an inflammatory state. This study examined the incidence of euglycemic diabetic ketoacidosis and potential opportunities for early diagnosis and management in patients undergoing pancreaticoduodenectomy. METHODS: A single-institution retrospective review of 350 patients who underwent pancreaticoduodenectomy between 2017 and 2020 was performed. Primary endpoints were peak beta-hydroxybutyrate levels, peak lactate levels, lowest pH, peak base deficits, and urinary output within the first 24 hours, postoperatively. Additional endpoints included incidence of postoperative pancreatic fistula, delayed gastric emptying, total complications, postoperative hospital length of stay, readmission rates, and changes in insulin regimen at discharge. RESULTS: Of the 350 cases reviewed, 39 (11.1%) patients developed euglycemic diabetic ketoacidosis. Male sex and pancreatic cancer were associated with a risk for euglycemic diabetic ketoacidosis (P < .05). Patients with euglycemic diabetic ketoacidosis had significantly higher peak beta-hydroxybutyrate levels than patients without euglycemic diabetic ketoacidosis (mean difference = 19.8 mg/dL, 95% confidence interval = 14.7-24.9, P < .001), and were nearly four times more likely to require insulin at discharge (odds ratio 3.8, 95% confidence interval = 1.1-13.0, P < .05). CONCLUSION: This is the first large descriptive study that investigates euglycemic diabetic ketoacidosis after pancreaticoduodenectomy. Euglycemic diabetic ketoacidosis after pancreaticoduodenectomy is associated with significantly higher beta-hydroxybutyrate levels and new or increased insulin requirement at discharge. Our study demonstrates potential markers for euglycemic diabetic ketoacidosis after pancreaticoduodenectomy, offering an opportunity to identify and successfully treat this disease in a timely manner.

Successful Treatment With Daptomycin of MRSA Empyema Complicated by Right-Sided Loculated Pleural Effusion Refractory to Vancomycin.

Empyema is a serious complication of pneumonia and has been reported to have a mortality rate of 8.7%. For methicillin-resistant Staphylococcus aureus (MRSA) empyema, treatment includes drainage and specific antibiotics such as vancomycin and linezolid. Strikingly, there are increasing incidences of empyema refractory to vancomycin and linezolid. Despite being inactivated in the lung parenchyma by pulmonary surfactant, daptomycin can penetrate the pleural space and may be better at treating MRSA empyema than vancomycin and linezolid. Some case reports have shown that daptomycin has been used to successfully treat MRSA empyema refractory to linezolid and vancomycin-resistant enterococcus (VRE) empyema. Here, we present a 26-year-old male with a past medical history of intravenous (IV) drug use, newly diagnosed HIV, HCV, and multifocal pneumonia complicated by a left-sided MRSA empyema that partially resolved with vancomycin and drainage. However, he subsequently developed a right-sided loculated pleural effusion. After the patient was switched to daptomycin with continued drainage, the right and left pleural effusions improved significantly. Once medically stable, he was discharged to a rehabilitation facility for further recovery. Our case report demonstrates that daptomycin could be considered as an effective treatment for MRSA empyema, particularly when refractory to vancomycin.